Nasopharyngeal carcinoma (NPC) is a malignant tumor in which the etiologic contribution of Epstein–Barr virus (EBV) is well established. However, similar to that of oropharyngeal carcinoma, some papers reported that human papilloma virus (HPV) contributed to the development of NPC in non-endemic regions. Previously, we conducted a study on HPV infection in patients with NPC between 1996 and 2015 in our department. The current study aims to evaluate the incidence and role of HPV infection in NPC pathogenesis using samples of NPC after 2015. Paraffin-embedded tumor samples from 26 patients with NPC who were treated at our department between 2015 and 2022 were analyzed. HPV polymerase chain reaction, p16 immunohistochemistry, HPV genotyping, and in situ hybridization for EBV-encoded RNA were performed to determine the viral infection status. Of the 26 patients, 19 (73%) were EBV-positive and HPV-negative, 1 (4%) was EBV-negative and HPV-positive, and 6 (23%) were negative for both EBV and HPV. The detection rate of HPV has slightly increased from 3% to 4% over the past decade. Although Japan is a non-endemic region for NPC, HPV infection is exceedingly rare and may have a limited role in NPC development in Japan. However, the detection rate of HPV has not significantly changed in the past decade, further supporting the view that HPV has a relatively small impact on the pathogenesis of NPC in Japan.

It is well known that a number of head and neck carcinomas are associated with HRAS mutations, and that several cancers with RAS mutations, such as lung cancer, have a poor prognosis. In this study, we evaluated the frequency of HRAS mutations in head and neck carcinomas and characterized the clinical and cell biological features of carcinomas with HRAS mutations. HRAS mutations at codons 12, 13, and 61, mutational hot spots, were evaluated in tissue specimens obtained from 119 Japanese patients treated at our institution. DNA was successfully extracted from 100 specimens, and sequencing was completed. An HRAS mutation was found in 8 (8.0%) cases: 5 (6.1%) out of 82 HNSCCs and 3 (16.7%) out of 18 salivary gland carcinomas. Mutations were found at codons 12 and 61, while none were found at codon 13, which differs from previous reports. The mutation-positive cases had a relatively poor prognosis, consistent with previous reports, and were more frequently accompanied by distant metastasis. HRAS knockdown with siRNA suppressed the in vitro migration ability of HRAS mutation-positive cells but not that of HRAS mutation-negative cells. In conclusion, a positive HRAS mutation could be an indicator of distant metastasis and poor prognosis, as well as a potential therapeutic target.

Objectives Nasal sinonasal inverted papillomas (SIP) are benign tumors with malignant potential that may progress to squamous cell carcinoma (SCC). Epidermal growth factor receptor (EGFR) expression is central to the development and malignant transformation of SIP, but the expression of its ligand, heparin-binding EGF-like growth factor (HB-EGF), and the regulators of HB-EGF expression have not been fully investigated. This study aimed to examine the expression of HB-EGF and its regulatory factors in SIP. Methods The expression of HB-EGF, EGFR, and phosphorylated EGFR (p-EGFR) was immunohistochemically examined in 32 patients with SIP, 3 with SIP-associated sinonasal squamous cell carcinoma (IPSCC), and 27 with de novo SCC arising in the sinonasal cavity (dnSCC). We also evaluated the expression of HIF-1α, an activator of ADAM12, which promotes the shedding of cytoplasmic membrane-bound HB-EGF from the cell surface. Results Among the 32 patients with SIP, most corresponded to Krouse stages T2-T3 and originated mainly in the maxillary or ethmoid sinus. All three cases of IPSCC were of the keratinizing type and classified as T4a. The 27 dnSCC cases were predominantly keratinizing type, arising chiefly in the maxillary sinus, and staged as T3-T4. HB-EGF and ADAM12 were expressed in all SIP and IPSCC cases, whereas the HB-EGF positivity rate was significantly lower in dnSCC (p < 0.05). EGFR and ADAM12 were broadly expressed across groups without significant differences, while p-EGFR expression was significantly higher in SIP and IPSCC compared with dnSCC (p < 0.05). Correlation analysis demonstrated a strong association between ADAM12 and HIF-1α, with weaker positive correlations observed between ADAM12 and HB-EGF, and between HB-EGF and p-EGFR. Conclusion HB-EGF expression is a characteristic feature of SIP. ADAM12 and HIF-1α may contribute to the distinctive upregulation of HB-EGF observed in SIP.